The growth and spread of cancer involves not just the malignant cells themselves, but also other "host" cells in the tumor microenvironment. For example, angiogenesis provides oxygen and nutrients to the cancer cells, and also provides a mechanism by which cancer cells metastasize. Inflammatory and immune cells play important cooperating roles by generating a hospitable environment for both tumor growth and metastasis. And stromal cells such as fibroblasts are often also sources of growth factors that promote tumor growth, as well as the proteases that degrade and remodel the extracellular matrix, and thus change the adhesive properties of the cancer cells. The goals of the Tumor Microenvironment Program are to understand the molecular basis for the cell/cell and cell/matrix interactions, cell adhesions and cell migrations that take place during tumorigenesis, and to define how to limit tumorigenesis with chemical or biological inhibitors of cancer cells and the tumor microenvironment. The Tumor Microenvironment Program (TME) was formed in 2007 by merging the Cell Adhesion &Extracellular Matrix Program with the Glycobiology Program, to take advantage of and further promote the synergies already existing in the two programs. The Program consists of 16 interactive laboratories, with expertise in structural biology, carbohydrate chemistry, cryoelectron microscopy, computational analyses, signal transduction, integrin biology and animal models of tumor growth and metastasis. The research in the Program can be described in terms of three overlapping themes: mechanisms and contributions of vascular and lymphoid components to tumor progression;the basic biology of metastasis (including the role of proteases);and the contribution of carbohydrate modifications to cancer invasion and progression. In addition, program members have an emerging interest in exploring the role of metabolism in cancer progression. In the last funding period, 3 new recruits were added to the Program, including the Program Leader, Dr. Sara Courtneidge. Members interact at a number of levels, including monthly faculty meetings, a recently established postdoc retreat, and through collaborative grants. Program funding is strong, with current total annual grant funding of $31.6MM ($18.3MM direct). Program Members currently lead or participate in 25 R01s (14 from NCI), 6 P01s (4 from NCI), and 9 U54/U19 grants (1 from NCI). Our productivity is reflected in our 430 publications since last review, and by 81 Program publications in 2008, with 12% intra- and 13% inter-programmatic collaborations.